DESCRIPTION: Recent research has suggested that a number of medications hold promise for improving outcomes in alcohol treatment. In particular, naltrexone and acamprosate act at different receptor sites and have each demonstrated an impact on alcohol consumption in animal and clinical trials. However, these drugs are typically given as an adjunct to behavioral interventions, despite little research to guide the specific nature of possible interactions between behavioral and pharmacological interventions. The present application proposes both a pilot study and a larger scale study for inclusion in the NIAAA cooperative agreement focusing on combined use of pharmacotherapies and behavioral interventions in the treatment of alcohol problems. A preliminary randomized trial is proposed that would evaluate the acceptability, safety, and clinical outcomes of naltrexone and acamprosate used in combination. The preliminary study will monitor side effects, adverse consequences, medication compliance, treatment retention, and changes in drinking, and craving during a 3-month trial period. The larger study is designed as a double-blind, placebo-controlled clinical efficacy trial of six-month intervention investigating the relative efficacy of two medications, naltrexone and acamprosate, used in combination with two behavioral interventions, one basic Motivation and Compliance Enhancement (MCE) and one where specific relapse preventive skills-training is added, MCE plus Integrated Relapse Prevention (MCE/IRP) across a twelve\month post-intervention follow-up. Subjects will be randomly assigned to one of four conditions combining the medications 1) naltrexone/acamprosate, 2) naltrexone placebo, 3) placebo acamprosate, and 4) placebo/placebo. All subjects will also receive a behavioral intervention to enhance motivation for chance (based on Motivational Enhancement Therapy) and medication compliance. Participants will be randomized to either eight sessions of Motivation and Compliance Enhancement or fifteen sessions of Integrated Relapse Prevention. Aims for the large study include: a) comparing, main and interactive effects of naltrexone, acamprosate, and behavioral interventions on outcome, b) evaluating medication compliance, treatment retention, and therapist effects medication clinical outcomes, and c) identifying patient attributes associated with differential response to the intervention combinations, thus suggesting, possible client-treatment matches.